Background: Retinoic acid induced 14 (RAI14 ), also known as NORPEG , is reported as being deregulated in non-small-cell lung cancer, together with having involvement in its cell proliferation as a super enhancer related gene. 
Purpose: The objective of this study was to investigate the role of RAI14  in the progression and metastasis of gastric cancer and explore the associated mechanism.
Materials and methods: GEPIA database was used to analyze the expression of RAI14  in gastric cancer. MNK45 and AGS cells were transfected with siRNA-RAI14  to block the expression of RAI14 . Cell Counting Kit 8 and colony formation assays were performed to measure cell proliferation. Cell migration and invasion capacities was examined by transwell assay. Apoptosis rate was detected using flow cytometry, and the protein levels of apoptosis-related proteins was determined using Western blot assay. Reverse-transcription PCR assay was used to detect the expressions of RAB31 .
Results: Gene expression profiling interactive analysis revealed that RAI14  was substantially upregulated in gastric cancer and higher expression of RAI14  was associated with worse prognosis. We also observed that the knockdown of RAI14  by siRNA-RAI14 transfection suppressed growth capacity of MKN45 and AGS cells. Also, RAI14  knockdown inhibited migration and invasion of MKN45 and AGS cells in vitro. Moreover, RAI14  knockdown was observed to accelerate cell apoptosis via downregulation of Bcl-2 and upregulation of Bax in MKN45 and AGS cells. Furthermore, downregulation of RAI14  inhibited the activation of Akt pathway, and activation of Akt by IGF-1 could restore the reduced proliferation induced by RAI14  knockdown. In addition, we found that RAI14  had a positive correlation with the RAB31  in gastric cancer by GEPIA reverse-transcription PCR and Western blot assays, and the reduced proliferation caused by RAI14  knockdown was restored by RAB31 .
Conclusion: RAI14  knockdown inhibited proliferation, migration and invasion and promoted apoptosis by downregulating the Akt pathway in gastric cancer cells, and RAB31  might be a downstream target gene of RAI14 , providing a novel sight into the molecular mechanism of RAI14  and a potential target for gastric cancer treatment.
Keywords: RAI14 , gastric cancer, progression, Akt pathway, RAB31